One of the most pressing needs in clinical oncology today is for a system which will allow selection of the most effective chemotherapeutic agent against an individual patient's tumor. The human tumor cloning system has potential for predicting which drug will or will not work against a patient's tumor. However, there are considerable problems with the conventional two layer agar system performed in 35 mm petri dishes. With support provided by this grant we have introduced a new system called the capillary cloning system. This system allows greater than 80 precent of patients' tumors to form colonies, increases cloning efficiencies, and requires fewer tumor cells than the conventional petri dish technique. A recently completed prospective clinical trial performed by our group randomized patients with a variety of refractory solid tumors to a selection of a single chemotherapeutic agent by this capillary cloning system versus a single agent selected by a clinician. That trial demonstrated a significantly higher response rate for the group treated according to the capillary results. However, there was no improvement in survival. These data (a higher response rate noted with the capillary system) provide a lead for further investigation. If the capillary system were used to select a combination chemotherapy regimen for patients, perhaps, that selection would have an impact on patients' survival. We propose a prospective randomized trial of the capillary cloning system for patients with extensive small cell lung cancer. Small cell lung cancer was chosen because it is a common disease (25,000 deaths/year), and while the response rate to standard combination chemotheraphy regimens is high (70-80%) the average survival is short (6 months). With this high response rate (of short duration) any impact of drug selection by the capillary system on response or survival should easily be detected. After stratification for important prognostic factors, patients with previously untreated extensive small cell lung cancer will be randomized to receive treatment with either a standard regimen (vincristine + Adriamycin + cytoxan) or treatment with a capillary cloning choice of drugs (most effective two or three agents in the capillary system). Tumor response, response duration, and patient survival will be assessed. This trial should define what place, if any, the capillary cloning system has in the care of the patient with extensive small cell lung cancer and may have implications for the utility of the capillary system in the care of patients with other types of malignancies.